Effects of PNU157706, a Dual 5α-Reductase Inhibitor, on Rat Epididymal Sperm Maturation and Fertility

The study examined the impact of PNU157706, a dual 5α-reductase inhibitor, on the fertility of adult male Sprague-Dawley rats. Over a 28-day treatment period, rats were given 10 mg/kg/day of PNU157706 or a vehicle. The treatment with PNU157706 resulted in a significant decrease in sperm motility and progressive motility, altered motion parameters, and a higher proportion of sperm with retained cytoplasmic droplets, indicating adverse effects on sperm morphology. The mating trials, which involved 8 males per treatment group paired with two females each, showed fewer successful pregnancies and an increased rate of preimplantation loss when females were mated with treated males, although the progeny that did result were unaffected. Despite no evidence of genetic damage to spermatozoa, testis weight, histology, or sperm counts, the study concluded that the reduced sperm motility and altered morphology due to PNU157706 treatment contributed to the observed subfertility in treated rats. This suggests the importance of both 5α-reductase isozymes in the epididymis and the potential use of dual 5α-reductase inhibitors in studying epididymal sperm functions and male contraception.